Cetuximab immunotherapy combination in head and neck cancer
- Conditions
- Squamous cell carcinoma of the head and neckCancerMalignant neoplasms of lip, oral cavity and pharynx
- Registration Number
- ISRCTN89314418
- Lead Sponsor
- The Christie NHS Foundation Trust
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped
- Sex
- All
- Target Recruitment
- 36
1. Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to local curative therapy with surgery or radiation therapy progressed beyond standard of care
2. Previous immunotherapy or cetuximab is permitted for part A (dose escalation) but not required. For Part B (expansion cohort), all patients must have progressed beyond treatment including immune checkpoint blockade (e.g. including but not limited to previous treatment targeting PD1/PDL1/CTLA4)
3. Able and willing to give valid written consent to provide newly acquired tumour tissue (preferred) or archival tissue. Determination of adequate tumour cell content to provide 25 slides will be undertaken by local site pathologist. Patients who do not meet this criteron may be considered eligible following discussion with the sponsor
4. For patients with oropharyngeal cancer (OPC) only: confirmed HPV status by p16 IHC, HPV PCR or ISH
5. Measurable disease by RECIST 1.1 (previously irradiated lesions must have progressed if to be used as marker lesions)
6. Written informed consent and any locally-required authorsation (e.g. HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
7. Age = 18 years at time of study entry
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Life expectancy of = 12 weeks
10. Body weight > 30 kg
11. Adequate normal organ and marrow functions as defined below:
11.1. Haemoglobin = 9.0 g/dL
11.2. Absolute neutrophil count (ANC) = 1.5 x 10^9/L
11.3. Platelet count = 100 x 10^9/L
11.4. Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician
11.5. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be = 5 x ULN
11.6. Serum creatinine CL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males: Creatinine CL(mL/min)= Weight(kg)x(140 - Age)]/[72 x serum creatinine(mg/dL)]
Females: Creatinine CL(mL/min)=[Weight(kg)x(140 - Age)]/[72 x serum creatinine(mg/dL)]x0.85
12. Evidence of post-menopausal status, negative urinary or serum pregnancy test of female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
12.1. Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinising hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilisation (bilateral oophorectomy or hysterectomy)
Full exclusion criteria with exceptions is located in the current study protocol.
1. Involvement in the planning and/or conduct of the study
2. Participation in another clinical study with an investigational product during the last 4 weeks
3. Concurrent enrolment in another clinical study, unless it is an observational clinical study or during the follow-up period of an interventional study
4. Receipt of the last dose of anti-cancer therapy < = 28 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator
5. Any unresolved toxicity NCI CTCAE Grade > = 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable
7. Major surgical procedure within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
8. History of allogeneic organ transplantation
9. Active or prior documented autoimmune or inflammatory disorders
10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic, congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, intersitial lung disease, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
11. History of another primary malignancy except for:
11.1. Malignancy treated with curative intent and with no known active disease > = 5 years before the first dose of IP and of low potential risk for recurrence
11.2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
11.3. Adequately treated carcinoma in situ without evidence of disease
12. History of leptomeningeal carcinomatosis
13. Brain metastases or spinal cord compression unless the patient is stable. Following radiotherapy and/or surgery of the brain metastases patients must wait 4 weeks following the intervention and before randomisation with imaging to confirm stability
14. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)> = 470 ms calculated from 3 ECGs
15. History of active primary immunodeficiency
16. Active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV RNA
17. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab
18. Receipt of live attenuated vaccine within 30 days prior to the first do
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method